Visit PLOS at IUMS 2014 in Montréal

Palais des Congrès. Image Credit: Gavin Schaefer, Flickr

We are pleased to announce that PLOS Pathogens will be exhibiting at the International Union of Microbiological Societies (IUMS), July 27th – August 1st in Montréal.

IUMS unites 3 international congresses of bacteriology and applied microbiology, mycology and eukaryotic microbiology, and virology. The conference will also host a number of bridging sessions on cross-discipline topics such as emerging infectious diseases and zoonoses, vaccines and anti-microbials, and host-pathogen and host-cell interactions. As PLOS Pathogens reflects the full breadth of research in pathogenesis, facilitating discussion between researchers studying bacteria, fungi, parasites, prions, and viruses, this conference is an excellent fit.

Please stop by booth #212 in the exhibition hall, next to the central coffee kiosk, Monday-Thursday 9:00-17:00. There you can meet Laura Ray and Max Vidrine, Publications Manager and Senior Publication Assistant of PLOS Pathogens, and Erica Kritsberg, Marketing Manager of PLOS Pathogens, PLOS Medicine, and PLOS Neglected Tropical Diseases. We’d be more than happy to discuss Open Access and the PLOS corpus, and we’ll be giving away PLOS memorabilia (while supplies last). You can also follow us on Twitter, we’ll be tweeting from @plospathogens using the #IUMS2014 hashtag.
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Millennium Development Goal 6: Measuring Progress

One of the most dramatic international responses to the Millennium Development Goals launched by then United Nations Secretary Kofi Annan in 2000 has been the global public health community’s response to MDG 6 “To combat AIDS, malaria and other diseases” [1].  For HIV/AIDS it led to President George W. Bush’s launch in 2003 of the President’s Emergency Plan for AIDS Relief (PEPFAR) in order to get people in resource-poor countries on antiretroviral drugs, and also to the ambitious Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), and later to large scale neglected tropical disease programs launched by the United States Agency for International Development (USAID),  British Department for International Development (DFID), the World Bank and World Health Organization (WHO) for administering rapid impact packages of anthelminthic drugs, together with azithromycin, in order to target seven of the most common NTDs [1].

DALYs: number by diseases and 21 regions in 2010 (in thousands) Image Credit: Hotez et al.

I choose the word “dramatic” because of the sheer size and scope of these programs.  Since 2000, more than $70 billion of overseas development assistance has been spent for mass drug treatments and other allied health interventions, such as antimalarial bednets, health education, and other health system strengthening measures.

This week two large multi-authored studies were published on studies that aim to measure the global public health progress on MDG 6.

The first is a landmark study by the Global Burden of Disease 2013 researchers led by Dr. Christopher Murray and the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, and supported by the Bill & Melinda Gates Foundation.  It provides an important snapshot in 2013 on where we stand with HIV/AIDS and malaria, as well as one additional “other disease,” namely tuberculosis.  The study analyzes a massive amount of data and I believe this Lancet publication will be a document that will be discussed for its public health and policy implications for a long-time to come.

Among its key findings are that through widespread use of antiretrovirals and other HIV/AIDS prevention measures, the number of new HIV/AIDS cases has decreased from 2.8 million new infections in 1997 to 1.8 million newly infected annually, with an almost two-thirds drop in the number of new pediatric AIDS cases.  The number of global deaths annually from HIV/AIDS has also started to fall from 1.7 million in 2005 to 1.3 million in 2013.  Similarly for malaria we have gone from 232 million new malaria cases in 2003 to 165 million in 2013, with a decrease from 1.2 million in 2005 to 855,000 deaths in 2013.  In contrast the gains in tuberculosis deaths have been more modest, but also muddled by the sharp rise in HIV-associated TB deaths.  Overall, I’m squarely in the Jeffrey Sachs camp on this one – overseas development assistance does indeed make a difference!

A second study published in PLOS Neglected Tropical Diseases does a deeper dive in the GBD Study 2010 with respect to neglected tropical diseases (NTDs).   Because integrated control of NTDs through mass drug administration and other measures did not begin until 2006 – and is only getting really ramped up in the last couple of years – it is too soon to say what the long term impacts will be on NTD control and elimination (and in terms of achieving London Declaration 2012 targets), but overall I am optimistic.  So far, the greatest declines (75 percent since 1990) have been for human African trypanosomiasis (HAT) – such that an elimination strategy may be feasible for Gambian HAT through case detection and treatment.    Another finding is the confirmation that many of the world’s NTDS occur in Asia and elsewhere outside of Africa.  At PLOS we have used the term “blue marble health” to address the high rates of diseases of poverty among the poor in wealthy countries.  In the coming months we hope to publish studies from the GBD Study 2013 on the NTDs and how they vary by region.

My additional takes on the findings from these two papers are as follows:  First, despite the gains through currently available interventions we are still going to need additional control tools before we consider eliminating the infections targeted by MDG 6.  I think a new generation of vaccines is going to be required.  Second, if we glance at the maps where HIV/AIDS and malaria are highest in Sub-Saharan Africa, they are in geographic regions where parasitic co-infections are also widespread, especially female genital schistosomiasis for HIV/AIDS and hookworm for malaria.  I believe that continued gains in the control of HIV/AIDS and malaria will require integrating parasite control into programs such as PEPFAR and GFATM.

The GBD Studies 2010 and 2013 are providing the essential bases for making evidence-based public health and policy decisions.  They will continue to inform us for a very long time!

  1. Hotez PJ (2013) Forgotten People Forgotten Diseases: The Neglected Tropical Diseases and their Impact on Global Health and Development Second Edition, ASM Press
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Evidently it’s Cholera Season

Just when the oppressive summer heat and humidity in South Asia seem no longer tolerable, especially to this Northern expatriate new to Bangladesh, the rains come, bringing relief in the form of cooler temperatures, fresh air, and sparkling trees and flowers.

What also comes with the monsoons is a reprieve from cholera.

Cholera is a form of acute watery diarrhoea, which spreads from person to person through food and water contaminated with the bacterium Vibrio cholerae. It is a miserable condition involving massive fluid loss and dehydration and left untreated can rapidly decline to death. Cholera is common in places with poor water and sanitation and sometimes causes large epidemics with thousands of people falling ill. Haiti’s cholera epidemic following the 2010 earthquake has killed more than 8000 people. The outbreak in South Sudan, currently affecting about 1500 people, is said to be worsening. In Bangladesh, where cholera is endemic, regular outbreaks are a fact of life and well-managed. Still, WHO estimates 3–5 million cases and up to 120,000 cholera deaths each year around the world.

At the public health research institution icddr,b (where I am an employee), our Dhaka Hospital sees about 300 people a day suffering from diarrheal diseases, but just before and after the monsoon this number can spike to as many as 1000 per day. Yes: 1000 patients per day, many with bodies ravaged by the dehydration and sometimes wasting that cholera can cause. Doubling the capacity of the hospital, beds known as ‘cholera cots’ occupy every available space and icddr,b erects massive tents to absorb the patient load. These tents can inhabit our entire parking lot.

TENT(Flood)14 AUG.07.12_Scaled

Image Credit: icddr,b


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PLOS launches Clinical Immunology Collection

Nathaniel Gore, Editorial Project Manager of PLOS Collections, on the launch of a new Clinical Immunology Collection

clinicalimmunology_allergies

Image Credit: NIAID/NIH, Wikimedia Commons / PLOS

Today PLOS launches a new Collection – the Clinical Immunology Collection. Following on from the successful redevelopment of the Synthetic Biology Collection, and responding to the commonly articulated request from our users that we provide more structured and efficient access to papers of interest in the PLOS corpus, the Clinical Immunology Collection is organized into several sub-disciplines, enabling researchers to easily locate the research they seek. To this end, the Clinical Immunology Collection launches today with sections on Allergies & Anaphylaxis and Tumor Immunology.

The Collection has been seeded with previously published PLOS content – from across the suite of PLOS journals – and will be expanded as new research and commentary is published by PLOS. Furthermore, the collection will see the addition of further Clinical Immunology subsections – including Immunodeficiency Syndromes, Autoimmune Conditions, Infectious Disease Immunology, Immunomodulatory Treatments and Transplant Immunology – and, later in the year, the addition of an Immunobiology Collection which will include sections on Cellular and Molecular Immunology, Evolutionary Immunology, Animal Models of the Human Immune System and Immune System Ontogeny.


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From One to One Million Article Views: Q&A with Author John Ioannidis

PLOS’s Erica Kritsberg interviews John Ioannidis about the success of his article “Why Most Published Research Findings Are False”, which reached one million views in April this year.

Iaonnidis

John Ioannidis

“Why Most Published Research Findings Are False”, the PLOS Medicine article by John Ioannidis, surpassed one million views late April 2014, the first PLOS article – research or other – to reach this milestone. First published Aug. 30, 2005, it has continued to influence thinking and inspire debate in the field and beyond.

To commemorate this achievement, Ioannidis, C. F. Rehnborg Professor in Disease Prevention, Professor of Medicine, of Health Research and Policy, and of Statistics at Stanford University (Stanford, CA, USA), spoke to us about the article’s background and impact to date.

What is the history behind the article? What compelled you to write about this topic?

JI: I had been thinking and working on the ideas behind this article for probably over a decade.  However, the first draft that integrated these ideas matured on the island of Sikinos (Greece) in early summer 2004. I remember working on it in a small balcony overlooking the cove of Alopronoia and telling Despina (my wife) all the time how excited I was about this work. I dare say it was some sort of very unique cognitive, but also aesthetic excitement.
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Book Review: The Adventure of the Cure That Wasn’t

Marzieh Ghiasi and Madhukar Pai from McGill University & McGill International TB Centre, Montreal, review “The Remedy” by Thomas Goetz

Robert Koch raised the hopes of millions of tuberculosis patients with his remedy (i.e. tuberculin) that turned out to be ineffective. Today, tuberculin is a widely used diagnostic test for latent tuberculosis infection (picture). Image credit: Madhukar Pai

Robert Koch raised the hopes of millions of tuberculosis patients with his remedy (i.e. tuberculin) that turned out to be ineffective. Today, tuberculin is a widely used diagnostic test for latent tuberculosis infection (picture). Image credit: Madhukar Pai

No image is more iconic of the Victorian age than that of a detective with a deerstalker cap, pipe, and magnifying glass roaming the dark streets of London in search of criminals and murderers. Hidden in plain sight, the real killers of the nineteenth century were infectious diseases such as tuberculosis, responsible for as many as a quarter of all deaths in that era.

In The Remedy (2014) science journalist Thomas Goetz recounts the stories of Robert Koch, the founder of modern bacteriology, and Arthur Conan Doyle, the physician-author of the Sherlock Holmes series. In two narratives that run in parallel and eventually intersect, Goetz introduces a cast of pioneering medical detectives, from Koch’s scientific rival Louise Pasteur, to Conan Doyle’s inspiration for Sherlock Holmes, Joseph Bell. We follow a search for causative agents, preventive vaccines, and remedies for some of the deadliest infections in the Victorian era. Goetz describes how the principles of evidence-based science and systematic experimentation guided these ground-breaking discoveries, and how overlooking these principles led to setbacks.
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EH!WOZA: Leaving the Lab and Addressing TB Stigmas and Taboos

Anastasia Koch, a molecular biology PhD student in South Africa talks about engaging the community with biomedical research.

Ikamva Youth on a visit to CBTBR labs

Lwazi Fanana, Ndilisa May, and Monwabisi Mkungela from Ikamva Youth visit MMRU labs
Image credit: EH!WOZA 2013

As a molecular biology – molecular mycobacteriology to be precise – PhD student, I never thought I’d be involved in the production of documentaries & online media resources. In the past few months, I’ve uncharacteristically found myself critiquing aesthetics in film and design owing to an involvement in a unique collaboration between biomedical scientists, artists, and a community not-for-profit organisation.

Let me begin with some background. I work in the Centre of Excellence for Biomedical TB Research (CBTBR) of the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town. My PhD research is focused on understanding the molecular determinants (and associated physiological implications) of drug resistance in Mycobacterium tuberculosis, the bacterium which causes tuberculosis (TB).
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I’m a Scientist with Learning Disabilities and That’s Okay!

Post doc Collin Diedrich discusses his experiences as a learning disabled scientist.

Image credit: Collin Diedrich

About a month ago, I was playing with my 3yr old niece, drawing pictures with Crayola Crayons. She pulled out a purplish color and asked me what it was. I dutifully read the name, as phonetically as I could, “MAG-A-NEAT-A… what the hell is MAG-A-NEAT-A?” We all laughed, and my brother (the dad) intervened: “It’s MA-GEN-TA.” I told my niece I probably am not the best person to read her these names. Also that I should learn to use better language around 3yr olds.

I read between a 6th and 9th grade level and have a language processing speed in the bottom 14% of the population. I have an unspecified reading disorder (DSM-IV 315.00) and learning disorder (DSM-IV 315.9). Despite these learning disabilities (LDs) and my love-hate relationship with Crayola Crayons, I have a PhD in molecular virology and microbiology and I am a second-year post doc at University of Cape Town. My life is not a mental contradiction.
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Everything You Always Wanted to See about Sex in Leishmania

Geneviève Lanotte (retired), Jean-Antoine Rioux (retired), and Jérémy Bouyer from CIRAD recount that cellular fusion in Leishmania was filmed in the 80s and provide the sex movie to the scientific community.

The title of our comment refers to the humorous title of the Review by Rougeron et al. (2010) on the sexuality of Leishmania: Everything You Always Wanted to Know about Sex (but Were Afraid to Ask)” in Leishmania after Two Decades of Laboratory and Field Analyses. In this paper, the authors present recent works challenging the dogmatic hypothesis of “dominant and ancient clonal reproductive mode”. Amazing animations already exist to illustrate the clonal reproduction cycle of Leishmania. Rougeron et al. (2010) refer to population genetics and experimental works but point out the “lack of clear evidence (experimental or biological confirmation) of sexuality in Leishmania parasites” and suggest using high-resolution imaging to capture a mating event. But what if a sex movie was already available?

Figure1

The sexuality of Leishmania: from fornicomastigotes (on the left) to a zygomastigote (on the right), recorded in the late 80s by Lanotte & Rioux. The full video is provided for the first time at the end of this comment.

Before satisfying our curiosity, let’s revisit some concepts.
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An Open Letter to the EMA from the AllTrials Steering Committee

AllTrials

AllTrials campaign
c/o Sense About Science
14A Clerkenwell Green
London EC1R 0DP

alltrials@senseaboutscience.org

 

Professor Guido Rasi
Director, European Medicines Agency
7 Westferry Circus
Canary Wharf
London E14 4HB

2nd June 2014

 

Dear Professor Rasi

Re: Draft Publication and access to clinical-trial data policy (EMA/240810/2013)

Hundreds of supporters of the AllTrials campaign contributed last year to the Agency’s consultation on its draft policy “Publication and access to clinical-trial data.” We welcomed the EMA’s proposals which would have seen Clinical Study Reports published proactively and openly in line with an Agency policy that the information in those reports should not generally be considered commercially confidential. We are now concerned that the most recent draft of the policy as shared with some stakeholders at meetings this month introduces barriers that will make it all but useless to independent researchers.

We understand that there are four areas of particular concern:

1. Clinical Study Reports will only be available for viewing on screen and cannot be saved, downloaded, printed, copied, annotated or shared in any way. This will make it nearly impossible for researchers to usefully scrutinise the documents. CSRs often contain thousands of pages of complex information. Research teams need to be able to share information and researchers have to be able to print or copy information such as outcome definitions, to make valid comparisons across studies. Your policy on access to CSRs as initially proposed could have made a genuine contribution to medical research. It now risks becoming a superficial and practically useless gesture.

2. The wording of the draft “Redaction Principles” policy is ambiguous, and where there is ambiguity, there is likely to be excessive redaction. For example, “statements/descriptions relating to objectives that are not supportive of a label claim and do not contribute to the overall benefit/risk evaluation” may be redacted. This would appear to suggest that any information on off-label uses of drugs will not be made available. While the Agency’s own use of these documents may be limited to a decision on one specific use of a treatment, in everyday clinical practice these same treatments are routinely and legally used by clinicians outside their marketing authorisation. This prescribing is based on published evidence that may be particularly vulnerable to dissemination bias, since evidence on off-label uses is frequently excluded from even voluntary codes of practice.

3. The “Redaction Principles” policy asks sponsors to submit two versions of a CSR from each trial: a standard version (CSR(a)) and a redacted version (CSR(b)). While this might be driven by a desire to lower the costs of transparency for the Agency, it puts primary responsibility for redacting in the hands of sponsors. How close CSR(a) is to CSR(b), and which parts are missing, may never be known to researchers granted access to CSR(b). Will there be an audit to explore whether redactions are proportionate or risk patient safety, and penalties for excessive redactions?

4. The Terms of Use contract contains clauses that seem to prioritise trial sponsors’ legal rights over researchers’ need to scrutinise and use information from CSRs to improve the evidence base for patient care. These supposed rights given to sponsors have never been established in law and are currently being debated in court cases in which the Agency is involved. Of greater concern, researchers will be asked to agree to a clause that allows trial sponsors to take direct legal action against the researcher for possible violation of the terms of use. Individual researchers are therefore being made vulnerable to protracted legal battles with large companies for infractions to these cumbersome rules. Since the rules themselves are poorly specified, these cases are likely to involve lengthy legal discussion. They will therefore introduce a new and unpredictable risk of high legal costs into routine academic work, effectively chilling researchers’ ability to use information relevant to patient care.
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